A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16ecto directed chimeric antigen receptors for recurrent ovarian cancer Journal Article


Authors: Koneru, M.; O'cearbhaill, R.; Pendharkar, S.; Spriggs, D. R.; Brentjens, R. J.
Article Title: A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16ecto directed chimeric antigen receptors for recurrent ovarian cancer
Abstract: Purpose: Recurrent platinum-resistant ovarian cancer has no curative options, necessitating the development of novel treatments, including immunotherapy. Rationale: Patient-derived T cells can be genetically modified to express chimeric antigen receptors (CARs) specific to tumor-associated antigens in an HLA-independent manner, with promising preclinical results. MUC16ecto is highly expressed on most epithelial ovarian carcinomas but at low levels on normal tissues, offering an excellent immunotherapeutic target for this cancer. CAR T cells further modified to secrete IL-12 show enhanced cytotoxicity, persistence, and modulation of the tumor microenvironment. Design: We propose a dose escalation phase I clinical trial for patients with recurrent MUC-16ecto+ ovarian cancer to test the safety of intravenous and intraperitoneal administration and the preliminary efficacy of autologous IL-12 secreting, MUC-16ecto CAR T cells containing a safety elimination gene. Innovation: This trial targets MUC-16ecto, a novel and promising tumor-associated antigen. This will be the first time CAR T cells are injected intraperitoneally directly into the site of the tumor within the abdomen in humans. Furthermore, the ability of genetically modified cells to secrete IL-12 will potentially enhance CAR T cell persistence and modulate the tumor microenvironment. For safety purposes, an elimination gene has been incorporated into the CAR T cells to mitigate any on-target, off-tumor or other unforeseen toxicity. © Koneru et al.; licensee BioMed Central.
Keywords: unclassified drug; advanced cancer; drug megadose; ovarian cancer; t lymphocyte; ovary cancer; cyclophosphamide; tumor antigen; dna modification; chimeric antigen receptor; adoptive transfer; adoptive immunotherapy; interleukin 12; tumor microenvironment; phase 1 clinical trial (topic); muc16; cytokine release syndrome; il-12; chimeric antigen receptors; article; muc 16 ecto
Journal Title: Journal of Translational Medicine
Volume: 13
Issue: 1
ISSN: 1479-5876
Publisher: Biomed Central Ltd  
Date Published: 2015-03-28
Start Page: 102
Language: English
DOI: 10.1186/s12967-015-0460-x
PROVIDER: scopus
PMCID: PMC4438636
PUBMED: 25890361
DOI/URL:
Notes: Export Date: 3 June 2015 -- Source: Scopus
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MSK Authors
  1. Renier J Brentjens
    269 Brentjens
  2. David R Spriggs
    324 Spriggs
  3. Mythili Koneru
    6 Koneru